Cell-sensory bioscaffolds, fabrication methods and applications of same

Abstract

A cell sensor and methods of using the cell sensor for differentiating types of cells. The cell sensor includes a sensing member having bioscaffolds comprising nanofibers/nanowires of titanate grown on a titanium sheet. The method includes preparing a cell sensor comprising a sensing member having bioscaffolds comprising nanofibers/nanowires of titanate grown on a titanium sheet; incubating the bioscaffolds with cells in an aqueous solution at an incubation temperature for a period of incubation time, wherein the cells in the aqueous solution include at least one of cancer cells, normal cells, stem cells, and neuron cells; and measuring electrical characteristics of the bioscaffolds to determine the types of the cells based on the measured electrical characteristics.

What is claimed is: 
     
         1 . Bioscaffolds, comprising:
 nanofibers/nanowires of titanate grown on a titanium sheet.   
     
     
         2 . The bio scaffolds of  claim 1 , wherein the nanofibers/nanowires of titanate are grown under a hydrothermal process. 
     
     
         3 . The bio scaffolds of  claim 1 , wherein the nanofibers/nanowires of titanate are entangled atop and self-assembled into scaffolds with concave nests on the titanium sheet. 
     
     
         4 . A cell sensor, comprising:
 a sensing member having bioscaffolds comprising nanofibers/nanowires of titanate grown on a titanium sheet, wherein in operation, the bioscaffolds are incubated with cells in an aqueous solution at an incubation temperature for a period of incubation time, wherein the cells in the aqueous solution include at least one of cancer cells, normal cells, stem cells, and neuron cells, and different types of cells produce differences in impedance change within certain frequencies on the bioscaffolds.   
     
     
         5 . The cell sensor of  claim 4 , further comprising an electrode coupled to the sensing member. 
     
     
         6 . The cell sensor of  claim 4 , wherein the nanofibers/nanowires of titanate are grown under a hydrothermal process. 
     
     
         7 . The cell sensor of  claim 4 , wherein the nanofibers/nanowires of titanate are entangled atop and self-assembled into scaffolds with concave nests on the sensing member. 
     
     
         8 . The cell sensor of  claim 4 , wherein different ratios of the cancer cells in the normal cells shifted the mixture's electrochemical signals quantitatively and reproducibly. 
     
     
         9 . The cell sensor of  claim 4 , wherein the cancer cells alter the surface charge-density of the bioscaffolds more than that of the normal cells while binding to the surface of nanofibers/nanowires of the bioscaffolds. 
     
     
         10 . A method for fabricating a cell sensor, comprising:
 providing a titanium sheet;   sonicating the titanium sheet in acetone at room temperature for a first period of time, and then rinsing the sonicated titanium sheet;   placing the rinsed titanium sheet in a NaOH solution to form a mixture thereof in a vessel and sealing the vessel;   hydrothermally treating the mixture of the titanium sheet and the NaOH solution sealed in the vessel in a heater at a predetermined temperature for a second period of time, thereby forming a sensing member having titanate nanowires-entangled scaffolds grown on the titanium sheet, and then cooling the vessel for a third period of time;   rinsing the sensing member until pH of the surface of the sensing member reaches about 7, and drying the rinsed sensing member in air; and   attaching an electrode onto an edge of the dried sensing member so as to form a cell sensor having a cell sensing area.   
     
     
         11 . The method of  claim 10 , wherein the first period of time is in a range of about 12 min to about 18 min. 
     
     
         12 . The method of  claim 10 , wherein the step of rinsing the sonicated titanium sheet is performed with distilled de-ionized (DDI) water. 
     
     
         13 . The method of  claim 10 , wherein the predetermined temperature is in a range of about 128° C. to about 300° C. 
     
     
         14 . The method of  claim 13 , wherein the second period of time is in a range of about 3.2 hrs to about 30 hrs and the third period of time is in a range of about 3.2 hrs to about 28.8 hrs. 
     
     
         15 . The method of  claim 10 , wherein the step of cooling the vessel is performed in air outside of the heater. 
     
     
         16 . The method of  claim 10 , wherein the step of rinsing the sensing member is performed with DDI water. 
     
     
         17 . The method of  claim 10 , wherein the step of attaching the electrode is performed by epoxy-gluing. 
     
     
         18 . The method of  claim 10 , further comprising, prior to attaching the electrode, scratching an edge surface of the sensing member to expose the titanium on which the electrode is attached. 
     
     
         19 . A method for differentiating types of cells, comprising:
 providing a cell sensor comprising a sensing member having bioscaffolds comprising nanofibers/nanowires of titanate grown on a titanium sheet;   incubating the bioscaffolds with cells in an aqueous solution at an incubation temperature for a period of incubation time, wherein the cells in the aqueous solution include at least one of cancer cells, normal cells, stem cells, and neuron cells; and   measuring electrical characteristics of the bio scaffolds to determine the types of the cells based on the measured electrical characteristics.   
     
     
         20 . The method of  claim 19 , wherein the measured electrical characteristics comprises impedance. 
     
     
         21 . The method of  claim 19 , wherein the electrical characteristics is dependent on at least one of the cells, the incubation temperature, the period of incubation time, and pH and components of the aqueous solution. 
     
     
         22 . The method of  claim 19 , wherein different types of cells produce differences in impedance change within certain frequencies on the bioscaffolds. 
     
     
         23 . The method of  claim 19 , wherein the cancer cells alter the surface charge-density of the bioscaffolds more than that of the normal cells while binding to the surface of nanofibers/nanowires of the bioscaffolds. 
     
     
         24 . The method of  claim 19 , wherein the aqueous solution contains phosphate buffer saline (PBS). 
     
     
         25 . The method of  claim 24 , wherein the PBS is prepared by charging DDI water and stirring charged DDI water with a magnetic stirrer while adding chemicals in the order of sodium chloride (NaCl), potassium chloride (KCl), sodium phosphate dibasic (Na 2 HPO 4 ), and potassium phosphate dibasic (KH 2 PO 4 ). 
     
     
         26 . The method of  claim 24 , wherein the pH of the aqueous solution is adjusted to in a range of about 6-8 by titrating with a hydrochloric acid (HCL) solution. 
     
     
         27 . The method of  claim 24 , wherein the aqueous solution contains about 100-1,000,000 cells/ml, preferably, about 1,000-10,000 cells/ml. 
     
     
         28 . The method of  claim 24 , wherein the incubation temperature is in a range of room temperature to about 37° C., and the period of incubation time is in a range of about 5-35 minutes. 
     
     
         29 . The method of  claim 24 , wherein a mixing ratio of the cancer cells to the normal cells in the aqueous solution ranges from about 1:1000 to about 1:5. 
     
     
         30 . The method of  claim 29 , wherein shift of impedance signals correlates linearly with the mixing ratio. 
     
     
         31 . The method of  claim 24 , wherein the aqueous solution further contains at least one of glucose and chemotherapeutic drug. 
     
     
         32 . The method of  claim 31 , wherein the chemotherapeutic drug comprises doxorubicin (DOX). 
     
     
         33 . The method of  claim 19 , wherein the cells includes one or more of MCF10A, MCF7 and MDA-MB231 and HCT116, wherein MCF10A is a normal human epithelial cell line, MCF7 is a human non-invasive epithelial breast cancer cell line, MDA-MB231 is a human invasive epithelial breast cancer cell line, and HCT116 is a colon cancer cell line. 
     
     
         34 . The method of  claim 19 , wherein the step of measuring the electrical characteristics of the bioscaffolds comprises:
 placing a reference electrode in the aqueous solution;   applying an AC signal having a frequency to the reference electrode; and   measuring the electrical characteristics of the bioscaffolds of the cell sensor accordingly.   
     
     
         35 . The method of  claim 34 , wherein the frequency is changed starting from about 30 kHz to about 1 MHz. 
     
     
         36 . The method of  claim 19 , further comprising:
 measuring the electrical characteristics of the bioscaffolds of the cell sensor in absence of the cells in the aqueous solution; and   comparing the measured electrical characteristics of the bioscaffolds of the cell sensor incubated the with the cells in the aqueous solution to the electrical characteristics of the bioscaffolds of the cell sensor in absence of the cells in the aqueous solution, so as to differentiate the types of cells.   
     
     
         37 . The method of  claim 19 , further comprising wiredly or wirelessly transmitting the measured electrical characteristics to a computer or a smart device for further processing and/or display. 
     
     
         38 . A method for selectively detecting different metabolic wastes of different live cells from digesting different nutrients or from reacting with different drugs over the time, comprising:
 placing a cell sensor comprising bioscaffolds in an aqueous solution at a temperature for a period of time, wherein the aqueous solution contains live cells, and nutrients and/or drugs; and   measuring electrical characteristics of the bio scaffolds to determine different metabolic wastes of different live cells from digesting different nutrients or from reacting with different drugs based on the measured electrical characteristics.   
     
     
         39 . The method of  claim 38 , wherein the measured electrical characteristics comprises impedance. 
     
     
         40 . The method of  claim 38 , wherein the aqueous solution contains phosphate buffer saline (PBS). 
     
     
         41 . The method of  claim 38 , wherein the electrical characteristics is dependent on at least one of the cells, the temperature, the period of time, and pH and components of the aqueous solution. 
     
     
         42 . The method of  claim 41 , wherein the nutrients comprise glucose. 
     
     
         43 . The method of  claim 41 , wherein the drugs comprises doxorubicin (DOX). 
     
     
         44 . A method for determining efficacy of drug-based reaction related to cell behavior, comprising:
 measuring electrical characteristics of bioscaffolds of a cell sensor placed in an aqueous solution containing live cells before and after the live cells are administrated with a drug, respectively; and   comparing the measured electrical characteristics before and after the live cells are administrated with the drug to determine the efficacy of the drug.   
     
     
         45 . The method of  claim 44 , wherein the measured electrical characteristics comprises impedance. 
     
     
         46 . A method for quantifying and characterizing bio-objects, comprising:
 providing a cell sensor comprising bioscaffolds;   incubating the bioscaffolds with bio-objects in an aqueous solution at a temperature for a period of time; and   measuring electrical characteristics of bioscaffolds to quantify and characterize bio-objects based on the measured electrical characteristics.   
     
     
         47 . The method of  claim 46 , wherein the measured electrical characteristics comprises impedance. 
     
     
         48 . The method of  claim 46 , wherein different types of bio-objects produce differences in impedance change within certain frequencies on the bioscaffolds. 
     
     
         49 . The method of  claim 46 , wherein the cancer cells alter the surface charge-density of the bioscaffolds more than that of the normal cells while binding to the surface of the bioscaffolds. 
     
     
         50 . The method of  claim 46 , wherein the bio scaffolds comprise titanate nanofibers/nanowires grown on a titanium sheet. 
     
     
         51 . The method of  claim 46 , wherein the bio-objects comprise cells, biological tissues, or bacteria. 
     
     
         52 . The method of  claim 46 , wherein the aqueous solution contains phosphate buffer saline (PBS). 
     
     
         53 . The method of  claim 46 , wherein the pH of the aqueous solution is adjustable.